Biophysical Model of Retraction Motor Neurons and Their Modification by Operant Conditioning

Author

Maria RasheedFollow

Author ORCID Identifier

0009-0009-1934-3218

Date of Graduation

5-2024

Document Type

Thesis (MS)

Program Affiliation

Neuroscience

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

John Byrne

Committee Member

Valentin Dragoi

Committee Member

Ruth Heidelberger

Committee Member

Neal Waxham

Committee Member

Kartik Venkatachalam

Abstract

Operant conditioning (OC) is a form of associative learning in which an animal modifies its behavior based on the consequences that follow that behavior. Despite its ubiquity, the underlying mechanisms of OC are poorly understood. Insights into the mechanisms of OC can be obtained by studying Aplysia feeding behavior as it can be modified by OC. This behavior is mediated by a central pattern generator (CPG) network in the buccal ganglia that contains a relatively small number of neurons. This CPG generates rhythmic motor patterns (BMPs) that move food into the gut by closing a tongue-like structure (i.e., radula) during the retraction phase of the BMP (Susswein and Byrne, 1988). Recent studies show that OC leads to increased intrinsic excitability in the major retraction motor neurons B6 and B9, while no significant changes were observed in B3 neurons. Using conductance-based modeling, this study examined OC-induced biophysical changes in B6 and B9. Neuron B4 makes an inhibitory chemical synaptic connection and is electrically coupled to B3, B6, and B9 retraction motor neurons. B4 excitability is reduced following OC. Neuron B51 is electrically coupled to B3, B6, and B9. The excitability of B51 is increased following OC. I hypothesized that presynaptic inputs from B4 and B51 premotor neurons are sufficient to account for the firing activity of B3, B6, and B9 during a BMP, and also that changes in excitability of B6 and B9 produced by OC are responsible for changes in B6 and B9 activity during BMPs. Therefore, I developed biophysical models of B3, B6, and B9 by incorporating ionic currents including I_Na, I_Kd, I_A, I_Kca, and I_leak. I incorporated these conductance-based models, and synaptic connections from B4 and B51, into the existing computational model of the CPG circuit and examined neuronal activity during simulated buccal motor programs (BMPs) and OC. However, simulations revealed that these synaptic connections did not drive firing in B3, B6, and B9. This finding indicates there must be other, not yet identified, neurons that drive B3, B6, and, B9. Therefore, I included an artificial synapse to help drive firing in these neurons. Simulations including this synapse suggested that alterations in motor neuron activity post-OC are produced by the changes in excitability of B6 and B9. This study provides important extensions to the existing model of the CPG and elucidates principles of the relationship between neuron circuitry and motor output, advancing our understanding of the neural mechanisms underlying operant conditioning and their impact on motor neuron function.

Keywords

computational, neuroscience, motor neurons, Aplysia, operant conditioning, buccal ganglia, CPG, Feeding behaviors, radula, protraction, retraction, bmps, ingestion, rejection